Role of scaffold proteins in the heterogeneity of glioblastoma.

Glioblastoma (GB) is a highly heterogeneous type of incurable brain cancer with a low survival rate. Intensive ongoing research has identified several potential targets; however, GB is marred by the activation of multiple pathways, and thus common targets are highly sought. The signal regulatory scaffold IQGAP1 is an oncoprotein implicated in GB.

Dimorphic glioblastoma with glial and epithelioid phenotypes: Clonal evolution and immune selection.

Purpose: Epithelioid glioblastoma is an unusual histologic variant of malignant glioma. The present study investigates both the genomic and transcriptomic determinants that may promote the development of this tumor.

Methods: Whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were performed on an epithelioid glioblastoma, along with a specific bioinformatic pipeline to generate electronic karyotyping and investigate the tumor immune microenvironment.

Prostate-Specific Membrane Antigen Expression in Meningioma: A Promising Theranostic Target.

Meningioma is the most common intracranial neoplasm, yet there is no effective therapy for recurrent/refractory meningiomas after surgery and radiation. Prostate-specific membrane antigen (PSMA) is an enzyme upregulated on endothelial cells of multiple neoplasms and is being investigated as a theranostic target. Until now, PSMA has not been studied in meningiomas.

Not Just an Anchor: The Human Filum Terminale Contains Stretch Sensitive and Nociceptive Nerve Endings and Responds to Electrical Stimulation With Paraspinal Muscle Activation.

Background: Neural components of the fibrous filum terminale (FT) are well known but are considered as embryonic remnants without functionality.

Objective: To investigate the ultrastructure of human FT specimens for sensory nerve endings and record paraspinal muscle activity on electrostimulation of the FT.

Methods: We prospectively investigated a cohort of 53 patients who underwent excision of the FT for the treatment of tethered cord syndrome.

Diseased Filum Terminale as a Cause of Tethered Cord Syndrome in Ehlers-Danlos Syndrome: Histopathology, Biomechanics, Clinical Presentation, and Outcome of Filum Excision.

Background: Patients with hypermobile Ehlers-Danlos syndrome (hEDS), a heritable connective tissue disorder, present frequently with symptoms of tethered cord syndrome (TCS) but without a low-lying conus. Currently, surgical treatment of such cases is controversial. Because connective tissue disorder affects fibrous structures, we hypothesized that a diseased filum terminale (FT) might cause TCS in hEDS, justifying surgical transection for treatment.

Evaluation of the Filum Terminale in Hereditary Equine Regional Dermal Asthenia.

The objectives of this study were to describe the anatomy, histology, and ultrastructure of the equine filum terminale (FT) and to describe the FT in hereditary equine regional dermal asthenia (HERDA), a model of human Ehlers-Danlos syndromes (EDS). Those humans suffer from tethered cord syndrome (TCS) caused by an abnormally structured FT wherein its attachment at the base of the vertebral column leads to long-term stretch-induced injury to the spinal cord. The pathophysiology of TCS in EDS is poorly understood, and there is a need for an animal model of the condition.

Abnormal spinal cord motion at the craniocervical junction in hypermobile Ehlers-Danlos patients.

Objective: The craniocervical junction (CCJ) is anatomically complex and comprises multiple joints that allow for wide head and neck movements. The thecal sac must adjust to such movements. Accordingly, the thecal sac is not rigidly attached to the bony spinal canal but instead tethered by fibrous suspension ligaments, including myodural bridges (MDBs).

Fatal Mucormycosis and Aspergillosis in an Atypical Host: What Do We Know about Mixed Invasive Mold Infections?

Mixed invasive mold infections (MIMIs) are considered rare. We present a case of fatal aspergillosis and mucormycosis in an elderly host with history of chronic lymphocytic leukemia (CLL) and potential mold exposures. Notably, he had no classic risk factors for IMI other than high-dose corticosteroids, which may be an important risk factor for (M)IMI, based on the current and previous reports.

A Transforaminal Endoscopic Approach for Treatment of a Lumbar Perineural Cyst: Technical Note.

Objective: Perineural cysts are a benign spine pathology but, when they become symptomatic and require surgical treatment, represent a significant challenge to the spine surgeon. Here we describe our experience with a novel endoscopic approach to the biopsy, drainage, resection of the cyst wall, and direct cyst fenestration to the subarachnoid space.

Methods: A transforaminal endoscopic approach to a large lumbar 2-3 perineural cyst is presented here in a 25-year-old patient.

Neuroprotective effects of inter-alpha inhibitor proteins after hypoxic-ischemic brain injury in neonatal rats.

Hypoxic-ischemic (HI) brain injury is one of the most common neurological problems occurring in the perinatal period. Hypothermia is the only approved intervention for neonatal HI encephalopathy. However, this treatment is only partially protective, has a narrow therapeutic time window after birth and only can be used to treat full-term infants.

Comparative transcriptomics of choroid plexus in Alzheimer's disease, frontotemporal dementia and Huntington's disease: implications for CSF homeostasis.

Background: In Alzheimer's disease, there are striking changes in CSF composition that relate to altered choroid plexus (CP) function. Studying CP tissue gene expression at the blood-cerebrospinal fluid barrier could provide further insight into the epithelial and stromal responses to neurodegenerative disease states.

Methods: Transcriptome-wide Affymetrix microarrays were used to determine disease-related changes in gene expression in human CP.

Enteric Pathologic Manifestations of Alpha-Synucleinopathies.

Background: Gastrointestinal (GI) symptoms are common in Parkinson disease (PD), often preceding neurological manifestations; however, early diagnostic utility of GI biopsies remains controversial. Studies suggest aberrant deposition of alpha-synuclein (α-syn) follows step-wise progression in central nervous system though histologic interpretation of normal and aberrant staining patterns have shown variable results. This study examines whether GI α-syn mRNA expression combined with standard α-syn immunohistochemical staining enhance the role of GI biopsy in PD.

Systemic infusions of anti-interleukin-1β neutralizing antibodies reduce short-term brain injury after cerebral ischemia in the ovine fetus.

Perinatal hypoxic-ischemic reperfusion (I/R)-related brain injury is a leading cause of neurologic morbidity and life-long disability in children. Infants exposed to I/R brain injury develop long-term cognitive and behavioral deficits, placing a large burden on parents and society. Therapeutic strategies are currently not available for infants with I/R brain damage, except for hypothermia, which can only be used in full term infants with hypoxic-ischemic encephalopathy (HIE).

Primary Spinal Epidural CIC-DUX4 Undifferentiated Sarcoma in a Child.

Primitive round- or spindle-cell EWSR1-negative undifferentiated sarcomas harboring CIC-DUX4 gene fusion are the most common form of Ewing-like sarcomas. These tumors primarily occur in peripheral soft tissues, but examples have been described within viscera and the brain. As far as we are aware, CIC-DUX4 positive primary epidural spinal sarcoma has not been reported.

The Orphan C2orf40 Gene is a Neuroimmune Factor in Alzheimer's Disease.

Expression of the orphan C2orf40 gene is associated with the aggregation of the neurofibrillary tangle-protein tau in transgenic mice, tumor suppression, the induction of senescence in CNS, and the activation of microglia and peripheral mononuclear leukocytes. This gene also encodes several secreted pro- and anti-inflammatory neuropeptide-like cytokines, suggesting they might be implicated in the inflammatory component(s) of Alzheimer's disease (AD). Accordingly, we evaluated human AD and control brains for expression changes by RT-qPCR, Western blot, and histological changes by immunolabeling.